Proposed clinical criteria for a memory loss disorder that is often misdiagnosed as Alzheimer's disease (AD), have been published.
The new criteria for limbic-predominant amnestic neurodegenerative syndrome (LANS) provide a framework for neurologists and other experts to classify the condition and offer a more precise diagnosis and potential treatments.
"In our clinical work, we see patients whose memory symptoms appear to mimic Alzheimer's disease, but when you look at their brain imaging or biomarkers, it's clear they don't have Alzheimer's. Until now, there has not been a specific medical diagnosis to point to, but now we can offer them some answers," senior investigator David T. Jones, MD, said in a release.
The proposed criteria and the research behind it were published online on July 17 in Brain Communications and will be presented on July 29 at the upcoming Alzheimer's Association International Conference in Philadelphia.
Already in Use
Predominant limbic degeneration has been linked to various underlying etiologies, older age, predominant impairment of episodic memory, and slow clinical progression, the investigators noted. However, they added, the neurologic syndrome associated with predominant limbic degeneration is undefined.
Developing clinical criteria and validating them "is critical to distinguish such a syndrome from those originating from neocortical degeneration, which may differ in underlying etiology, disease course, and therapeutic needs," the investigators wrote.
The newly proposed clinical criteria apply to LANS, which is "highly associated with limbic-predominant age-related TDP-43 encephalopathy but also other pathologic entities."
The criteria incorporate core, standard, and advanced features including older age at evaluation, mild clinical syndrome, disproportionate hippocampal atrophy, impaired semantic memory, limbic hypometabolism, absence of endocortical degeneration, and low likelihood of neocortical tau with highest, high, moderate, and low degrees of certainty.
"A detailed history of the clinical symptoms, which may be supported by neuropsychological testing, with the observation of disproportionate hippocampal atrophy and limbic degeneration on MRI/FDG yields a high confidence in a diagnosis of LANS, where the most likely symptom-driving proteinopathy is TDP-43 and not Alzheimer's associated proteins," the first author, Nick Corriveau-Lecavalier, PhD, assistant professor of neurology and psychology at Mayo Clinic, Rochester, Minnesota, told Medscape Medical News.
To validate the criteria, the investigators screened autopsied patients from Mayo Clinic and Alzheimer's Disease Neuroimaging Initiative cohorts and applied the criteria to those with a predominant amnestic syndrome and those who had AD neuropathologic change, limbic-predominant age-related TDP-43 encephalopathy, or both pathologies at autopsy.
"The criteria effectively categorized these cases, with Alzheimer's disease having the lowest likelihoods, limbic-predominant age-related TDP-43 encephalopathy patients having the highest likelihoods, and patients with both pathologies having intermediate likelihoods," the investigators reported.
"Patients with high likelihoods had a milder and slower clinical course and more severe temporo-limbic degeneration compared to those with low likelihoods," they added.
Corriveau-Lecavalier said the team is currently analyzing longitudinal cognitive and imaging trajectories in LANS over several years. "This will help us better understand how LANS and Alzheimer's differ in their sequence of symptoms over time."
It is important to understand that memory symptoms in old age are not "unequivocally" driven by Alzheimer's and that LANS progresses more slowly and has a better prognosis than AD, he noted.
In addition, in vivo markers of TDP-43 are "on the horizon and can hopefully make their way to human research settings soon. This will help better understand the underlying molecular etiologies causing LANS and associated symptoms," he said.
Corriveau-Lecavalier said the LANS criteria are ready for clinical use by experts in neurologic care. These criteria can be used to inform not only diagnosis but also prognosis, where this syndrome is associated with slow and mild progression and a memory-dominant profile.
He added that "the new criteria are also routinely used in our practice to make decisions about anti-amyloid treatment eligibility."
Commenting on the research for Medscape Medical News, Rebecca M. Edelmayer, PhD, Alzheimer's Association senior director of scientific engagement, said the research "exemplifies the great need to develop objective criteria for diagnosis and staging of Alzheimer's and all other types of dementia and to create an integrated biological and clinical staging scheme that can be used effectively by physicians."
"Advances in biomarkers will help to differentiate all types of dementia when incorporated into the diagnostic workup, but until those tools are available, a more succinct clinical criteria for diagnosis can be used to support a more personalized medicine approach to treatment, care, and enrollment into clinical studies," said Edelmayer, who wasn't involved in the research.
The research was funded in part by the National Institutes of Health and by the Robert Wood Johnson Foundation, the Elsie & Marvin Dekelboum Family Foundation, the Liston Family Foundation, the Edson Family, the Gerald A. and Henrietta Rauenhorst Foundation, and the Foundation Dr Corinne Schuler. Corriveau-Lecavalier and Edelmayer had no relevant conflicts of interest.